Human phagocytes have at least two classes of receptors that mediate phagocytosis of opsonized particles. While Fc receptors constitutively mediated phagocytosis, the function and membrane expresion of complement receptors are under regulatory control. Considerable progress has been made in the last year in understanding the mechanisms involved in control of plasma membrane expression and function fo these receptors. We first showed that a variety of cell activators induce upregulation of complement receptors. Intracellular latent pools of receptors exist for complement receptors and the intracellular location of one class of complement receptors was elucidate. Receptor upregulation was also noted to be dependent upon calcium mobilization. Regulation of receptor expression per se did not enable cells to mediate phagocytosis. We also found two proteins that modify the phagocytic function of complement receptors. We studied the effect of one of these proteins, fibronectin as well as phorbol esters the behavior of complement receptors in neutrophils. Phorbol esters but not fibronectin induce ligand-independent internalization of CR1 by a cytoskeletal and temperature dependent mefchanism. These agents also perturbate the association of CR1 with cytoskeleton. Synthetic diocylglycerol also induce receptor internalization. Both phorbol esters and synthetic diacylglycerols augment phagocytosis even through plasma membrane expression of CR1 is decreased. We also studied the role of calcium in these processes. We propose that the physiologic activation of CR1 may occur via polyphosphoinositied metabolism thorugh the avtivation of protein kinase C and calcium mobilization. Understanding the regulation of function of complement receptors is of importance both from the point of view of cell biology as well as disease pathogensis.